The most debilitating and fatal form of malaria is caused by the complex protozoan parasite, Plasmodium falciparum. Resistance to available drugs for the treatment of malaria was first recognized in the United States during the Vietnam conflict and has since been shown to be increasing in geographical range, severity, and prevalence. Laboratory and epidemiological evidence now suggest that Plasmodium falciparum has acquired multiple drug resistance that is largely independent of the chemical class of drugs to which the parasites are exposed. With multiple drug resistance in falciparum malaria coupled with an increase in worldwide tourism, the prevention and treatment of malaria is rapidly emerging as a major health issue in the United States. Consequently, it is of critical importance to develop new drugs for the treatment of falciparum malaria.
Cryptolepis sanguinolenta, a shrub indigenous to West Africa, has been used by Ghanaian traditional healers for many years for the treatment of fevers, including malaria. (Boye, G L and Ampofo, O., Proceedings of the First International Symposium on Cryptolepine, Univ. of Sci. and Tech, Kumasi, Ghana (1983)). A root decoction of Cryptolepis has been used clinically by Oku Ampofo at the Centre for Scientific Research into Plant Medicine since 1974 for the treatment of malarial fever, as well as for the treatment of bacterial infections (Boye, G L and Ampofo, O. Proceedings of the First International Symposium on Cryptolepine, Univ. of Sci. and Tech, Kumasi, Ghana (1983)).
There is sufficient evidence to suggest that the root extracts of Cryptolepis have antipyretic, antibacterial and antimalarial activity. However, the antimalarial component or components of the Cryptolepis extract are unknown.
In 1978, Dwuma-Badu, et al. isolated two alkaloids, cryptolepine and quindoline, from the roots of the West African plant Cryptolepis sanguinolenta. This began a series of investigations into the constituents of C. sanguinolenta (Dwuma-Badu, et al. (1978) J. Pharm. Sci. 67: 433-434). Cryptolepine had previously been synthesized (Fichter, F. and Boehringer, F. (1906) Ber. Dtsch. Chem. Ges. 39: 3932-3942) and chemically analyzed. Biological evaluation of cryptolepine has demonstrated that the alkaloid possesses antimicrobial, antipyretic, antiinflammatory, and hypotensive properties (Boakye-Yiadom, K. and Heman-Ackah, S. M. (1979), J. Pharm. Sci. 68: 1510-1514; Bamgbose, S.O.A. and Noamesi, B. K. (1981) Planta Med. 41: 392-396; Raymond Hamet (1937) C.R. Soc. Biol., 126: 768-770; Noamesi, B. K. and Bamgbose, S.O.A. (1980) Planta Med., 39: 51-56). A report by Peters in 1981 indicated that cryptolepine had positive activity against rickettsia-like organisms but failed to support the clinical evidence of the anti-malarial activity of the Cryptolepis extract (quoted in Boye, G L and Oku Ampofo (1983) on page 37.
Use of the crude extract for the treatment of malaria is inefficient, unreliable, and cumbersome. It also has the significant disadvantage of involving the culture and manipulation of a West African plant, rather than the utilization of an isolated pure, active component.